PURPOSE: This study examined a developmental model that links affect-regulation difficulties in childhood with three dimensions of alexithymia in adolescence (difficulty identifying feelings, difficulty describing feelings, and externally-oriented thinking) and substance use and depression in adulthood, while accounting for cumulative contextual risk in childhood, and testing potential gender moderation. METHODS: Multiple group path analyses were conducted using data from the Northern Finland Birth Cohort 1986 (N = 6,963). Analyses used data collected during prenatal/birth, childhood, adolescence, and young adulthood periods. RESULTS: Our examination of early precursors for alexithymia indicated that the associations of affect-regulation problems in childhood with alexithymia were stronger for girls, potentially putting girls with affect-regulation difficulties in childhood at higher risk for developing alexithymia in adolescence. The associations of cumulative contextual risk in childhood with alexithymia, substance use disorder, and depression diagnosis in adulthood were significant for both girls and boys. Our findings in regard to substance use and depression disorders revealed that alexithymia in adolescence predicted depression diagnosis in adulthood, particularly due to a contribution from the alexithymia domain of “difficulties identifying feelings.” However, none of the alexithymia domains was directly associated with substance use disorder in adulthood. CONCLUSIONS: Our study contributes to research that links alexithymia with difficulties in affect regulation and cumulative contextual risk in childhood, yielding findings that may be relevant for preventive interventions.